Chem 263
Sept 22, 2009
Conjugated Dienes and Colour Continued
Beta-carotene (depicted below) is the orange-red colour in carrots.
β-carotene
Xanthophylls
Xanthophylls are oxygenated carotene molecules. Zeaxanthin, shown below is purple.
OH
HO
In the below example, astaxanthin, a blue-green pigment in algae, is converted to
astascene with the addition of heat, water and oxygen. Astascene is red in colour and
contains an enol functional group. Crustaceans (eg. lobsters) eat algae in their natural
habitat and therefore ingest astaxanthin. When a lobster is cooked, it turns a bright red
colour, which is mainly due to the formation of astascene.
O
OH
HO
O
Astaxanthin
H2O, O2
Heat
secondary
alcohol
O
OH
Enol
HO
O
Ketone
Astascen
Hemoglobin (red colour in blood) and chlorophyll A (green colour in plants) are two
more examples of conjugated molecules that absorb light and serve critical functions.
The Chemistry of Vision
Not all conjugated molecules are coloured (need 7 conjugated double bonds). They also
make up the light sensitive substances responsible for the visual systems of organisms. A
key component of our vision arises from the body’s ability to synthesize Vitamin A from
beta-carotene (shown below) in which the C40 beta-carotene is broken down into the C20
vitamin A.
OH
Vitamin A
In the liver, vitamin A is further oxidized to retinal, a process in which the primary
alcohol functionality is oxidized to the aldehyde.
OH
[O]
H
O
Retinal
This bond changes from
trans to cis
In the eye, retinal reacts with a protein called opsin to give rhodopsin, the visual pigment
that is the actual light sensitive substance. Isomerization of the C11-C12 bond from trans
to cis causes a conformational change in the 3D structure of the protein that results in
nerve impulses being sent to the brain which are perceived as vision.
Further oxidation of the aldehyde to a carboxylic acid in retinal yields retinoic acid, a
chemical messenger in the body, which provides signals for fetal development.
H
O
[O]
O
OH
Retinoic acid
Conversion of the C13 double bond in retinoic acid to the cis conformation gives the drug
Accutane, which is an anti-acne drug. It has teratogenic properties (i.e. can cause
malformations and other birth defects)
2
O
11
6
OH
13
8
4
cis-trans
conversion
HO
Accutane
O
Radical Halogenation
Substitution Reaction:
Note that if Hydrogens are not shown, other groups could also be attached for the
following 2 examples
X2
X = Cl, Br
low concentration
C
C
hv or heat
H
X
O
NBS
C
hv or heat
H
+
C
NH
Br
O
In this case, light is usually used
succinimide
O
NBS = N-Bromosuccinimide
N
Br
Know this reagent!
O
H 3C
C
+
C
H
Br
low Br2 concentration,
heat or light
H
Br
H 2C
Br
H
C
H
H
H
reversible
H 3C
H
C
C
H
Br
Br
H
CH3
Br
C
C
Br
H
high Br2 concentration
H
+
C
H
HBr
In the above example, the cationic intermediate is formed in both cases. If the bromine
concentration is small, it is unlikely that the very small concentration of the Br will
interact with the cation in order to react, so the cation just reacts back to the initial
starting material and the first reaction predominates. If the bromine concentration is
high, then it becomes much more likely that the Br will react with the cation and the
second reaction predominates.
There is another reaction that competes with the first reaction, but it results in the same
product:
Br2
Br
H
Br
H
Br
H
H
C
H
C
+
HBr
H
C
H
C
C
H
C
H
H
H
conjugated radical
stable
H
H
C
H
C
H
resonance
H
C
H
C
C
H
C
H
H
H
The C with the radical has sp2 geometry
The radical lines up with the p orbitals of the π bond
H
H
H
Br
C
H
C
H
C
H
C
H
rare, Br
concentration is small
C
H
C
H
Br
H
H
much more likely
Br
H
C
H
Br
H
C
This reaction is an allylic halogenation,
specifically it’s an allylic bromination
Br
C
Br
H
Diels-Alder Reaction
The Diels-Alder reaction was discovered in 1928 by Kurt Alder and Otto Diels. Both
later won the Noble Prize in 1950 for their discovery.
The Diels-Alder reaction consists of a conjugated diene in cisoid form reacting an alkene
(also called an olefin, or for these reactions a dienophile because it is ‘diene loving’).
When heated, it forms two new carbon-carbon bonds in a single step and forms a cyclic
molecule (a cyclohexene). The reaction is theoretically reversible but the stability of the
product drives the reaction to completion. The Diels-Alder reaction is an example of a
[4+2] electrocyclic reaction. The [4+2] refers to the 4 π-electrons from the diene and the
2 π-electrons from the dienophile. The mechanism of the Diels-Alder reaction occurs
through a pericyclic process in which the π-electrons move in a cycle or ring.
C
C
C
C
Diene
C
C
= Heat
Dienophile
C
C
C
C
C
C
Diels-Alder adduct
Although the transoid conformation of dienes is more favoured, the cisoid and transoid
conformations are in equilibrium, so as the cisoid reacts with the alkene, more is formed.
The mechanism is concerted, which means that all the bonds form and break at the same
time (an SN2 reaction is also concerted). As a result, the reaction is also stereospecific,
which means that the stereochemistry of the starting materials determines the
stereochemistry of the products. Starting from achiral substrates, a racemic mixture of
stereoisomers can be formed. The diene and dienophile line up in such a way that the
endo product rather than the exo product is formed. Endo and Exo are used to indicate the
relative stereochemistry of a bicyclic structure. A substituent on one bridge is said to be
endo if it is anti (trans) to the smaller of the two bridges and exo if it is syn (cis).
A one-carbon bridge
Exo substituent
(syn to smaller bridge)
R
R
A two-carbon bridge
Endo substituent
(anti to smaller bridge)
An example to apply to other systems is the Diels-Alder reaction of furan (diene) and
maleic anhydride (dienophile). In this reaction, the dienophile approaches the 5membered ring furan from the bottom side, producing an endo Diels-Alder adduct.
O
O
furan
H
H O
H O
H
maleic anhydride
O
O
O
O
O
O
H H
O
O
Endo product
The exo product, which is not favored and not formed, would arise in the following
manner.
O
O
furan
H
maleic anhydride
O
O
O
O
O
O
H H
H O
Exo product
O
O
H
H O
Example of possible Diels-Alder adducts in Nature
The Spanish fly (Cantharis vesicatoria) produces the molecule cantharidin, which
contains an exo Diels-Alder product with an anhydride functional group.
O
O
O
O
Canthardin
Example of Predicting Stereochemistry
The following example uses 2Z, 4E-hexadiene (diene) and cyclopentene (dienophile) to
produce an endo product. As shown before with the furan and maleic anhydride reaction,
the stereochemistry of the endo product can be predicted. The methyl group at C6 is
similar to that of the H in furan and therefore will be pointing down. The position of the
C1 methyl group is similar to that of the oxygen in furan and therefore will point up in
the endo product (by convention drawn away from (outside of) the cyclohexene ring).
6
H
1
2Z,4E-hexadiene
H
cyclopentene
Endo product
Lecture Outline 2 (Posted on the website)
Aromatic Compounds
Benzene was first isolated in 1825 by Michael Faraday. Its structure was later determined
by Joseph Loschmidt and F. August Kekule to contain a cyclic, 6-membered ring
containing alternating single and double bonds with 6 π-electrons. The name benzene
comes from benzoic acid.
H
H
C
C
H
C
C
H
C
C
O
H
OH
H
Benzene (C6H6)
Benzoic acid
There are a few ways of drawing benzene. It is seen as alternating double and single
bonds, a central circle or as the Greek symbol φ (phi).
H
H
C
C
H
C
C
H
H
C
C
H
H
H
Where
H
H
H
H
Phenyl group
The central circle is used to represent the resonance within the aromatic ring
Eg.
Br
Br
Br
Br
Br
resonance
Br
1,2-dibromobenzene
Benzene’s resonance makes it 36 kcal/mol more stable than what is calculated for
‘cyclohexatriene’.
resonance
cyclobutadiene
Is cyclobutadiene also aromatic?
No! It is actually anti-aromatic (to be described later)
It is extremely unstable
Rules for Aromaticity:
• Cyclic and conjugated about the ring
• Planar
• 4n + 2 π electrons, where n is a positive integer (ie. 1, 2, 3, 4, etc.)
4n+2 rule:
Benzene has 6 π electrons, so for this rule n = 1 (4*1+2 = 6)
Cyclobutadiene has 4 π electrons, which does not allow n to be an integer
4n+2 = 4, n = 0.5 which is not an interger, therefore this cannot be an aromatic
molecule